There are many different lesions of the oral mucosa including malignancies of various types that can jeopardize the health of the patient. It is estimated that there will be 30,000 new cases of oral cancer in the United States in 1986. Efforts aimed at identification of possible etiologic agents are clearly warranted. Papillomaviruses are one of the many kinds of viruses found in the mouth. Because of their tropism for epithelium, they are excellent candidates as etiologic agents of benign and malignant lesions of the oral mucosa. This study will investigate the role of human papillomavirus in lesions of the oral mucosa. Tissues from patients with various oral lesions will be analyzed prospectively and retrospectively for evidence of papillomavirus infection. New types of papillomavirus will be cloned where indicated. In vitro studies of cellular transformation will examine the oncogenic potential of the human papillomaviruses found in the mouth. The approaches to these problems will be through direct studies of human tissues by staining with antibodies to papillomavirus antigens and by hybridization to DNA of known types of papillomavirus. To investigate the oncogenicity of human papillomavirus, cultured cells will be transfected with human papillomavirus DNA alone or in combination with other agents such as herpes simplex virus and various chemical carcinogens. Cell lines established from oral cancers will be examined for the presence of human papillomavirus nucleic acid sequences to provide further evidence for the oncogenic potential of these viruses. It is hoped that this study will increase the understanding of the etiology of several types of lesions of the oral mucosa, especially oral malignancies. This research is compatible with research objective FO6 of the National Institute of Dental Research.